{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:36:23Z","timestamp":1787016983475,"version":"build-2736575974"},"reference-count":36,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T00:00:00Z","timestamp":1731542400000},"content-version":"unspecified","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Bristol Myers Squibb","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,9,30]]},"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To estimate thresholds for defining meaningful within-patient improvement from baseline to weeks 13\u201324 and interpreting meaningfulness of between-group difference for the non-transfusion-dependent beta-thalassaemia patient-reported outcome (NTDT-PRO) tiredness\/weakness (T\/W) and shortness of breath (SoB) scores. A secondary objective was to determine the symptom severity threshold for the NTDT-PRO T\/W domain to identify patients with symptomatic T\/W.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>\n                      Pooled blinded data from the phase 2, double-blind, placebo-controlled, randomised BEYOND trial in NTDT (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03342404\">NCT03342404<\/jats:ext-link>\n                      ) were used. Anchor-based analyses supplemented with distribution-based analyses and empirical cumulative distribution function (eCDF) curves were applied. Distribution-based analyses and receiver operating characteristic curves were used to estimate between-group difference and symptomatic thresholds, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Greece, Italy, Lebanon, Thailand, the UK and the USA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>Adults (N=145; mean age 39.9 years) with NTDT who were transfusion-free \u22658 weeks before randomisation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measures<\/jats:title>\n                    <jats:p>Score changes from baseline to weeks 13\u201324 in PROs used as anchors (correlation coefficient \u22650.3): NTDT-PRO T\/W and SoB scores, Patient Global Impression of Severity, Functional Assessment of Chronic Illness Therapy\u2013Fatigue (Fatigue Subscale, item HI12 and item An2) and Short Form Health Survey version 2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The eCDF curves support the use of estimates from the improvement by one level group for all anchors to determine the threshold(s) for meaningful within-patient improvement. Mean (median) changes from these groups and estimates from distribution-based analyses suggest that a \u22651-point reduction in the NTDT-PRO T\/W or SoB domains represents a clinically meaningful improvement. Meaningful between-group difference threshold ranges were 0.53\u20131.10 for the T\/W domain and 0.65\u20131.15 for the SoB domain. The optimal symptomatic threshold for the T\/W domain (by maximum Youden\u2019s index) was \u22653 points.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The thresholds proposed may support the use of NTDT-PRO in assessing and interpreting treatment effects in clinical studies and identifying patients with NTDT in need of symptom relief.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-085234","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T07:15:16Z","timestamp":1731568516000},"page":"e085234","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Identifying thresholds for meaningful improvements in NTDT-PRO scores to support conclusions about treatment benefit in clinical studies of patients with non-transfusion-dependent beta-thalassaemia: analysis of pooled data from a phase 2, double-blind, placebo-controlled, randomised trial"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct03342404","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03342404","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8515-2238","authenticated-orcid":false,"given":"Ali T","family":"Taher","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled M","family":"Musallam","sequence":"additional","affiliation":[{"name":"Center for Research on Rare Blood Disorders (CR-RBD), Burjeel Medical City, Abu Dhabi, UAE"},{"name":"Division of Hematology\/Oncology, Department of Pediatrics, Weill Cornell Medicine, New York city, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vip","family":"Viprakasit","sequence":"additional","affiliation":[{"name":"Siriraj Research Hospital, Mahidol University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonis","family":"Kattamis","sequence":"additional","affiliation":[{"name":"First Department of Paediatrics, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Lord-Bessen","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aylin","family":"Yucel","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shien","family":"Guo","sequence":"additional","affiliation":[{"name":"Evidera, Waltham, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5255-2777","authenticated-orcid":false,"given":"Christopher G","family":"Pelligra","sequence":"additional","affiliation":[{"name":"Evidera, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan L","family":"Shields","sequence":"additional","affiliation":[{"name":"Adelphi Values, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeevan K","family":"Shetty","sequence":"additional","affiliation":[{"name":"Celgene International S\u00e0rl, a Bristol\u2013Myers Squibb Company, Boudry, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mrudula B","family":"Glassberg","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Madison, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana Moro","family":"Bueno","sequence":"additional","affiliation":[{"name":"Celgene International S\u00e0rl, a Bristol\u2013Myers Squibb Company, Boudry, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Domenica","family":"Cappellini","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda Policlinico Hospital, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,11,14]]},"reference":[{"key":"2025121407474311000_14.11.e085234.1","doi-asserted-by":"crossref","DOI":"10.1186\/1750-1172-5-11","article-title":"Beta-thalassemia","volume":"5","author":"Galanello","year":"2010","journal-title":"Orphanet J Rare Dis"},{"key":"2025121407474311000_14.11.e085234.2","unstructured":"Taher A , Musallam K , Cappellini MD . 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